Clinical Efficacy of Telitacicept in Sjögren's Disease With Interstitial Lung Disease

This is a prospective, open-label, single-center cohort study to evaluate the real-world effectiveness of Telitacicept compared with conventional immunosuppressive therapy in patients with primary Sjögren's disease associated interstitial lung disease. A total of 60 patients with confirmed interstitial lung disease by high-resolution computed tomography will be enrolled and allocated into two cohorts based on the treatment regimen selected by their treating physician according to clinical indications and patient preference: one cohort receiving Telitacicept 160 mg subcutaneously once weekly and the other receiving conventional immunosuppressive agents.

Treatment effectiveness will be evaluated over 24 weeks. The primary outcome is the change from baseline in forced vital capacity percent predicted (FVC% predicted) at Week 24. Secondary assessments include DLCO% predicted, total lung capacity, HRCT changes quantified using the Warrick score, KL-6, ESSDAI. Changes in B-cell subsets and related biomarkers will be explored for associations with pulmonary outcomes.

• Telitacicept 160mg (Drug): The study duration was 24 weeks, with the experimental group receiving subcutaneous injections of Telitacicept once weekly for a total of 24 weeks.
• Conventional treatment (Drug): Conventional treatment with methylprednisolone (≤ 40 mg/day) and other immunosuppressive agents (including but not limited to cyclophosphamide, tacrolimus, sirolimus, cyclosporine, leflunomide, azathioprine, mycophenolate mofetil, hydroxychloroquine, tripterygium glycosides, methotrexate, and sulfasalazine). Treatment restrictions: The use of immunosuppressants was limited to a maximum of three agents throughout the 24-week period, and dose adjustments from baseline were restricted to within 30%.

Primary outcomes

• Change From Baseline in Forced Vital Capacity Percent Predicted at Week 24 [At baseline and at week 12,24]: FVC will be measured using standardized pulmonary function testing and expressed as the percentage of the predicted value. The outcome will be calculated as Week 24 FVC% predicted minus baseline FVC% predicted. The adjusted between-group difference will be estimated between the telitacicept and conventional-treatment cohorts.

Secondary outcomes

• Change From Baseline in Diffusing Capacity for Carbon Monoxide Percent Predicted at Week 24 [Baseline, Week 12, and Week 24]: The outcome will be calculated as Week 24 DLCO% predicted minus baseline DLCO% predicted.
• Change From Baseline in Total Lung Capacity at Week 24 [Baseline, Week 12, and Week 24]: Total lung capacity will be measured by standardized pulmonary function testing. Both the observed value and percent predicted, where available, will be recorded.
• Change From Baseline in HRCT Warrick Score at Week 24 [Baseline and Week 24]: HRCT abnormalities will be assessed using the Warrick scoring system. The severity score ranges from 0 to 15 and is based on five abnormalities: ground-glass opacity (1 point), irregular pleural margins (2 points), septal or subpleural lines (3 points), honeycombing (4 points), and subpleural cysts (5 points). For each abnormality, extent is scored according to the number of bronchopulmonary segments involved: 1-3 segments (1 point), 4-9 segments (2 points), and more than 9 segments (3 points), giving a total extent score of 0-15. The Warrick total score is the sum of severity and extent scores and ranges from 0 to 30, with higher scores indicating greater ILD involvement.
• Change From Baseline in Serum Krebs von den Lungen-6 at Week 24 [Baseline, Week 12, and Week 24]: Serum Krebs von den Lungen-6 (KL-6) concentration will be measured as a biomarker associated with interstitial lung disease activity and severity.
• Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index at Week 24 [Baseline, Week 12, and Week 24]: The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) will be assessed at each specified visit. The outcome is Week 24 ESSDAI minus baseline ESSDAI.

Other outcomes

• Changes in Peripheral B-cell Subsets and Related Biomarkers [Baseline, Week 12, and Week 24]: Changes from baseline in total B cells, B-cell subsets, immunoglobulins, and soluble CD25 will be evaluated. Associations between immunologic changes and changes in FVC% predicted, DLCO% predicted, Warrick score, and KL-6 will be explored.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Age 18 to 70 years, male or female.
2. Diagnosis of primary Sjögren's Syndrome meeting the 2016 ACR/EULAR classification criteria.
3. Confirmed diagnosis of Interstitial Lung Disease by High-Resolution Computed Tomography (HRCT).
4. Stable doses of corticosteroids and immunosuppressants (e.g., mycophenolate mofetil) for at least 1 week prior to enrollment.
5. Willing and able to provide written informed consent

Exclusion Criteria:

1. Allergy: Known allergy or hypersensitivity to Telitacicept or any of its excipients.
2. Concomitant Autoimmune Diseases: Diagnosis of other systemic autoimmune diseases besides Sjögren's Syndrome, such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Systemic Sclerosis (SSc), Mixed Connective Tissue Disease (MCTD), or ANCA-associated vasculitis. (Note: Secondary Sjögren's Syndrome is not excluded on this basis alone, but the primary condition must be considered).
3. Laboratory Abnormalities (at Screening):

   Hematology:

   Hemoglobin (Hb) < 85 g/L. White Blood Cell count (WBC) < 3.0 × 10\^9/L. Neutrophil count (NEUT) < 1.5 × 10\^9/L. Platelet count (PLT) < 80 × 10\^9/L.

   Liver Function:

   Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 2.5 × the upper limit of normal (ULN).

   Total bilirubin (TBIL) > 1.5 × ULN.

   Kidney Function:

   Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m². Or serum creatinine (Cr) > 1.5 × ULN.
4. Significant Organ Diseases or Comorbidities:

   Cardiovascular: Myocardial infarction or unstable angina within the past 6 months; uncontrolled hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg); pulmonary arterial hypertension with evidence of right heart failure.

   Respiratory: Presence of other significant lung diseases (e.g., COPD, asthma, pulmonary embolism, active pulmonary tuberculosis).

   Gastrointestinal: Active peptic ulcer, gastrointestinal bleeding, or pancreatitis.

   Malignancy: History of any malignancy within the past 5 years (excluding successfully treated basal cell carcinoma of the skin or in-situ cervical carcinoma).

   Psychiatric: Severe mental illness (e.g., severe depression, schizophrenia) or cognitive impairment that may interfere with compliance.
5. Prior/Concomitant Medications:

   Use of rituximab, belimumab, TNF inhibitors (e.g., etanercept, adalimumab), or ther biologic agents (e.g., IL-6, IL-17, IL-23 inhibitors) within 3 months prior to screening.

   Participation in another interventional clinical trial (receiving investigational drug or device) within 4 weeks prior to screening.
6. Active Infection:

   Presence of an active infection requiring systemic anti-infective treatment at screening.

   Active tuberculosis (positive T-SPOT.TB or TST with chest X-ray/CT findings suggestive of active disease).

   Positive HIV antibody. Positive Hepatitis B surface antigen (HBsAg), or positive Hepatitis B core antibody (HBcAb) with detectable HBV DNA.

   Positive Hepatitis C antibody with detectable HCV RNA.
7. Special Populations:

   Women who are pregnant or breastfeeding. Women of childbearing potential who are unwilling or unable to use highly effective contraceptive methods from screening until at least 3 months after the last dose of study drug.

   Patients planning to undergo major surgery during the study period.
8. Other Situations:

Inability to cooperate with pulmonary function tests (e.g., due to severe cognitive impairment or dyspnea).

Any condition that, in the opinion of the investigator, makes the patient unsuitable for participation in this study (e.g., poor compliance, inability to understand study procedures).

• Yuan Jia, Principal investigator, Peking University Institute of Rheuamotology and Immunology